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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Among 7,697 nondrinkers with no history of cardiovascular disease after 4 years, the 6% who had begun moderate alcohol consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for women) had a 38% lower chance of developing cardiovascular disease than did persistently nondrinking controls. However, among the 0.4% who began heavier drinking, cardiovascular risk increased. (Am J Med [March 2008] 121:201)[CrossRef]
A novel experimental system has been described involving transplantation of pancreatic islets into the anterior chamber of the eye, where they can be repeatedly assessed in vivo by fluorescence imaging by laser-scanning microscopy, permitting observation of their vascularization, cellular composition, and beta cell stimulus–response coupling. (Nat Med [published online ahead of print March 7, 2008])
In a prospective study of factors related to falls in elderly diabetes patients, low glycohemoglobin in insulin users increased the risk of falling (OR 4.4 [95% CI, 1.3–14.5] comparing A1C 6% vs. >8%), but lower A1C was unassociated with falls in those using oral hypoglycemic medications. (Diabetes Care [March 2008] 31 (3):391)
In 839 obese patients, those treated with the endogenous cannabinoid inhibitor rimonabant had greater reductions in body weight and improvements in serum lipids and hsCRP than those given placebo; but there were no differences in atheroma volume measured by coronary intravascular ultrasound after 18 months of treatment. (JAMA [April 2, 2008] 299 (13):1547)
In a multicenter trial of 543 patients with coronary disease and type 2 diabetes, atheroma volume measured by coronary intravascular ultrasound increased after 18 months of glimepiride treatment by 0.7% (95% CI, 0.3% to 1.1%) and decreased 0.2% (95% CI, –0.6% to 0.3%) with pioglitazone. (JAMA [April 2, 2008] 299 (13):1561)
In a 44-week, randomized, open-label study of 418 patients with type 2 diabetes randomly assigned to either once daily insulin glargine or to insulin lispro three times per day, the mean hemoglobin A1c decreases were comparable, –1.7% and –1.9%, respectively. However, insulin glargine improved fasting glucose values more, caused less hypoglycemia, and was associated with better patient satisfaction, whereas postprandial glucose values were lower throughout the day with insulin lispro. (Lancet [March 29, 2008] 371 (9618):1073)
A meta-analysis of 2.2 million single nucleotide polymorphisms in 10,128 individuals identified six new gene regions linked to type 2 diabetes, including JAZF1, CDC-123-CAMK1D, TSPAN8-LGR5, THADA, ADAMTS9, and NOTCH2. (Nat Genet [published ahead of print March 30, 2008])
In 5,968 people, lipoprotein (a) levels were associated with future risk of coronary heart disease over many decades, independent of the effects of several established cardiovascular risk factors such as age, sex, smoking status, blood pressure, total cholesterol, triglycerides level, diabetes mellitus, and body mass index. (Arch Intern Med [March 24, 2008] 168 (6):598)
Early-onset paternal obesity, but not maternal obesity, increased the odds of elevated serum alanine aminotransferase (ALT) levels in offspring (OR:1.8; 95% CI:1.1–2.9), suggesting a genetic predisposition to developing elevated serum ALT and possibly nonalcoholic fatty liver disease. (Gastroenterology [April 2008] 134 (4):953)
Despite undergoing 6 months of hibernation, wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid osteopenia related to inactivity, possibly pointing to future prevention and treatment options for osteoporosis. (Comp Biochem Physio [February 2008] 149 (2):20)
Loss of IGF signaling in mice caused severe misrouting of olfactory sensory axons away from the lateral olfactory bulb, suggesting that IGFs play a role as axonal guidance cues for olfactory neurons. (Neuron [March 27, 2008] 57:847)[CrossRef]
Concurrent use of selective serotonin reuptake inhibitors and tricyclic antidepressants was associated with a doubling of type 2 diabetes risk (adjusted OR:1.9; 95% CI, 1.4–2.7) compared to tricyclics alone. (J Diab Res Clin Pract [January 2008] 79 (1):61)
In mouse models, estrogen receptor β acted in concert with brain-derived neurotrophic factor to promote neural plasticity and protection against acoustic trauma, potentially paving the way for possible therapeutic strategies against hearing loss. (J Clin Invest [April 2008] 118 (4):1563)
Longitudinal analysis of 6,583 people for over three decades revealed that those with the greatest centralized distribution of fat in midlife had nearly a threefold increased risk of developing dementia (HR: 2.7; 95% CI, 2.3–3.3). (Neurology [published ahead of print March 26, 2008])
In C. elegans, insulin/IGF-1-like signaling directly inhibited longevity-promoting factor SKN-1, in addition to FOXO protein DAF-16, further emphasizing the growth factor's role in aging. (Cell [March 21, 2008] 132:1025)[CrossRef]
A 5-year longitudinal study of 100,000 people in the British South Tees area found that organized care for patients with diabetic foot disease found that major diabetes-related lower extremity amputations were decreased, whereas non-diabetes-related lower extremity amputations increased. (Diabetes Care [March 2008] 31 (3):459)
In a 3.5-year longitudinal study of 2,407 people, higher serum TSH concentration was linked to body weight in both sexes. (Arch Intern Med [March 24, 2008] 168 (6):587)
In a 3-year longitudinal study of 11,262 middle-aged adults, those with type 2 diabetes had lower predicted forced vital capacity and FEV1 than non-diabetics (96 vs. 103%, P<0.001 and 92 vs. 96%, P<0.001, respectively). (Diabetes Care [April 2008] 31 (4):741)
In patients with a body mass index of 40 or higher undergoing bariatric surgery, genetic mutations in the fat mass and obesity associated gene (FTO) and the insulin induced gene 2 (INSIG2) were associated with morbid obesity. (Arch Surg [March 2008] 143 (3):235)
Expression analysis of 23,720 RNA transcripts in blood and adipose tissue of 1,675 Icelandic subjects confirmed that gene expression variation affects the risk of becoming obese. (Nature [March 27, 2008] 452:423)[CrossRef]
In 261 premenopausal women with reduced libido and low serum free testosterone levels, a single, daily 90 uL dose of transdermal testosterone for four months improved self-reported sexual satisfaction by a mean of 0.8 satisfactory sexual events per month (P=0.04). (Ann Int Med [April 15, 2008] 148 (8):569)
Breast Milk's Protective Effect in Type 2 Diabetes
Breastfeeding may have a protective effect against the development of type 2 diabetes, according to research recently published in the March 2008 issue of Diabetes Care. Previous studies in Pima Indians showed that individuals with type 2 diabetes were less likely to have been breastfed, hinting at breastmilk's protective effect.
Elizabeth Mayer-Davis, Ph.D., a nutrition professor now at the University of North Carolina at Chapel Hill, and her colleagues from the Universities of South Carolina and Colorado analyzed this effect by surveying 247 individuals 10–21 years of age in three ethnic populations known to be at high risk for diabetes—non-Hispanic whites, Hispanics, and African Americans.
Performing a case–control study of 80 adolescents with type 2 diabetes compared to 167 controls, the team found that the breast-feeding rate was lower in youths with diabetes than in controls, at 39 vs. 78% in non-Hispanic whites, 50 vs. 84% in Hispanics, and 20 vs. 27% in African Americans, respectively. This protective effect was still observed even after the removal of confounding factors such as family history, birthweight, presence of maternal diabetes, and maternal body mass index and health habits during pregnancy.
"We did see evidence of a protective effect in all three groups and no evidence statistically that there was a different effect in the three groups," said Mayer-Davis.
Protection may be due in large part to its previously documented ability to reduce the risk of developing obesity in childhood. This ability may be due to the potential to over-feed bottle-fed infants, or the different composition of proteins and fats between breast milk and formula.
"The nutrient composition of breast milk actually changes over the course of a given feeding. That's probably there for some evolutionary reason having to do with signaling for satiety,"explained Mayer-Davis. "In formula, you get what you get from the beginning to end of the feeding. The composition is the same and that's not true of breastmilk"
According to Mayer-Davis, her findings could aid in the future prevention of type 2 diabetes. "This could be a real nice way to move families towards primary prevention in the next generation," said Mayer-Davis. "There's plenty of good reasons to breastfeed, this may be just one more reason to encourage breastfeeding in these high-risk ethnic groups."
Mayer-Davis plans to expand on this study by investigating infant feeding practices with a large number of kids with diabetes.
Examples of uncontrolled confounding variables that need to be considered include post-weaning diet in infancy and late childhood, and physical activity, according to Michael S. Kramer, M.D., Scientific Director of the Institute of Human Development, Child and Youth Health, Canadian Institutes of Health Research, and Professor at McGill University, Montreal, Canada. (Diabetes Care [March 2008] 31 (3):470)
Thyrotropin Triggers Birdsong
Marrying old and new scientific techniques, researchers have shown how thyroid stimulating hormone (TSH) may regulate a bird's seasonal reproductive behavior, a function previously not attributed to this hormone.
Over 40 years ago, Dr. Peter Sharp, Ph.D., FRSE, an avian reproductive biologist at the Roslin Institute, University of Edinburgh, Scotland, used electrolytic lesions in the bird brain to identify a small part of the hypothalamus that determines day length differences, a trigger for Spring breeding behavior that is manifested by singing. How this region becomes activated in the Spring remained a mystery for most of his career.
Now his research has come full circle. Collaborating with a Japanese team led by animal physiologist Takashi Yoshimura, Ph.D., at Nagoya University, Japan, functional genomics technology was used to get at the answer. Using DNA microarrays to scan 28,000 genes from the Japanese quail (Coturnix japonica), which had received varying lengths of light corresponding to short and longer days, the team discovered that two genes were switched on in cells on the surface of the hypothalamus called the pars tuberalis, after birds had seen 14 hours of light. One of these was a transcription factor for a photoreceptor while the other was TSH.
The finding of the hormone in this particular region runs counterintuitive to what has been previously known about its location and function. Normally the hypothalamus secretes thyroid releasing hormone, which stimulates the pituitary to secrete TSH. TSH then stimulates the thyroid to make triiodothyronine and thyroxine, hormones that are involved in metabolism and thermogenesis.
Sharp and Yoshimura were stunned. Their research showed that TSH, now found to be produced in the pars tuberalis, travels into the hypothalamus where it indirectly prompts the pituitary to secrete gonadotropins which stimulate the sex organs to grow. "We could not believe that thyrotropin may act on the central nervous system to stimulate the reproductive neuroendocrine system to initiate breeding, because thyrotropin is best known as a pituitary hormone which regulates the thyroid gland. Unconsciously, we are adhered to common sense," said Yoshimura, who along with Sharp, reported this discovery in an article in the March 20, 2008 issue of Nature.
"That's the opposite flow of direction to what we've been normally taught about as students," said Andrew London, Ph.D., an animal biologist from the University of Manchester in England who was not involved in the research.
When the researchers infused TSH directly into the brains of birds exposed to short day lengths, the birds went into full breeding condition. In other words, said Loudon, "Thyroid hormones are the equivalent of summer day length."
Since humans also have TSH cells in the pars tuberalis, figuring out the photoperiod pathway in birds may have implications for humans suffering from seasonal affective disorder or infertility issues said Sharp, who after retirement decided to go back and perform some of the bench work needed for the article.
"It's been a thrill for me to see finally something that I've discovered all those years ago now having a cellular explanation," said Sharp. (Nature [March 20, 2008] 452:317)[CrossRef]
Growth Hormone Confers No Athletic Benefit
Marion Jones, Barry Bonds, Mark McGwire, and Roger Clemens—once admired for their athletic prowess—have all fallen under the cloud of illegal steroid use to boost their performance.
Although research data suggests that androgenic anabolic steroid hormones increase muscular strength, it is unclear whether growth hormone (GH) enhances athletic ability. Previous studies have shown that exogenous GH therapy in GH-deficient adults and healthy elderly adults results in increased lean mass and decreased fat mass. However, some say that its strength-enhancing properties have been exaggerated.
In a recent meta-analysis performed by Hau Liu, M.D., MBA, MPH, a physician at the Santa Clara Valley Medical Center in San Jose, California, and colleagues, which looked at 27 studies and 303 participants aged 13–45 years of age who took GH, a compound revered for its "ripped muscle" effect and possible increase in stamina, no athletic benefit was conferred.
The study, published online on March 18, 2008, in the Annals of Internal Medicine, concluded that while lean body mass increased in people who took GH, strength and exercise capacity did not, and those taking the hormone appeared to experience more soft tissue swelling and fatigue than controls. No difference was seen in VO2 between the two groups, and lactic acid, an indicator of muscle fatigue, was significantly higher in GH-treated participants in 2 of the 3 studies that evaluated this outcome.
This meta-analysis, however, is not the definitive answer to the question, as regimens evaluated in the research setting are likely different from regimens used by athletes in the "real world." Athletes may use human GH in higher doses and for longer periods of time than those used in the examined studies. In fact, researchers previously thought that testosterone had no positive effects on athletic performance. This was later disproved when studies using higher doses of testosterone were used. Athletes may also use GH in combination with other drugs such as androgenic steroids, insulin, and antiestrogens.
"It's an important first step but it's certainly not the final word," said Liu of his own study. "If we really want to understand if GH can help you hit a baseball farther or throw a ball faster we need to do studies that mimic those types of scenarios with the real-world regimens that athletes are taking. And those studies have not been done."
Bradley Anawalt, M.D., professor of medicine and staff physician at the VA Puget Sound Health Care System, Seattle, Wash., and consulting member for the U.S. Anti-Doping Agency, agreed.
"The scientific data suggests that GH is not helpful and may be harmful to athletes and normal young men and women, but the data are really scanty," he said. "We don't really know what is happening to these athletes when they use really large doses of GH over a long period of time." (Ann Intern Med [published ahead of print March 18, 2008])
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Milestones in Endocrinology |
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In the Journal 25 Years Ago |
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"We conclude that phosphate therapy may accelerate regeneration of erythrocyte 2,3-DPG but in the relatively small number of patients studied it had no demonstrable influence on tissue oxygenation or clinical response to low-dose insulin therapy of DKA. Furthermore, the exaggeration of hypocalcemia seen in phosphate-treated patients may be reason for caution in the use of such therapy."
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